Bioresponsive immune-booster-based prodrug nanogel for cancer immunotherapy.
10.1016/j.apsb.2021.05.016
- Author:
Xianbin MA
1
;
Shaochen YANG
2
;
Tian ZHANG
1
;
Shuo WANG
2
;
Qichao YANG
2
;
Yao XIAO
2
;
Xiaoxiao SHI
3
;
Peng XUE
1
;
Yuejun KANG
1
;
Gang LIU
3
;
Zhi-Jun SUN
2
;
Zhigang XU
1
Author Information
1. Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, School of Materials and Energy & Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices, Southwest University, Chongqing 400715, China.
2. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
3. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
- Publication Type:Journal Article
- Keywords:
5-ALA, 5-aminolevulinic acid;
5-FU, 5-fluorouracil;
ALKP, alkaline phosphatase;
ALT, alanine aminotransferase;
APCs, antigen-presenting cells;
AST, aminotransferase;
ATP, adenosine triphosphate;
AUC, area under curves;
Bioresponsive;
CLSM, confocal laser scanning microscope;
CPT-11, irinotecan;
CRE, creatinine;
CRT, calreticulin;
Ce6, chlorin e6;
Chemotherapy;
DAMPs, damage-associated molecular patterns;
DCs, dendritic cells;
DDSs, drug delivery systems;
DLN, draining lymph nodes;
DM NGs, doxorubicin-based mannose nanogel;
DOC, docetaxel;
DOX, doxorubicin;
DTT, d,l-dithiothreitol;
Doxorubicin;
FCM, flow cytometry;
FDA, Fluorescein diacetate;
GEM, gemcitabine;
GSH, glutathione;
H&E, hematoxylin-eosin;
HCPT, 10-hydroxy camptothecin;
HCT, hematocrit;
HGB, hemoglobin concentration;
HMGB1, high migrating group box 1;
ICB, immune checkpoint blockade;
ICD, immunogenic cell death;
ICG, indocyanine Green;
IHC, immunohistochemistry;
ITM, immunosuppressive tumor microenvironment;
Immunogenic cell death;
Immunotherapy;
LDH, lactate dehydrogenase;
LYM, lymphocyte ratio;
MAN, mannose;
MCHC, mean corpuscular hemoglobin concentration;
MCSs, multicellular spheroids;
MFI, mean fluorescence intensity;
MPV, mean platelet volume;
Mannose;
NGs, nanogels;
Nanogel;
OXA, oxaliplatin;
P18, purpurin 18;
PDI, polydispersity index;
PLT, platelets;
PTX, paclitaxel;
Prodrug;
RBC, red blood cell count;
RDW, variation coefficient of red blood cell distribution width;
TAAs, tumor-associated antigens;
TAM, tumor-associated macrophages;
TGF-β, transforming growth factor-β;
TMA, tissue microarrays;
TME, tumor microenvironment;
Urea, urea nitrogen;
WBC, white blood cell count;
irAEs, immune-related adverse events
- From:
Acta Pharmaceutica Sinica B
2022;12(1):451-466
- CountryChina
- Language:English
-
Abstract:
The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.
